Retrospective, multicentric study of 180 children with cytochrome C oxidase deficiency
Language English Country United States Media print-electronic
Document type Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't
PubMed
16326995
DOI
10.1203/01.pdr.0000190572.68191.13
PII: 01.pdr.0000190572.68191.13
Knihovny.cz E-resources
- MeSH
- Cytochrome-c Oxidase Deficiency diagnosis genetics mortality MeSH
- Child MeSH
- Infant MeSH
- Humans MeSH
- Membrane Proteins MeSH
- DNA, Mitochondrial genetics MeSH
- Mitochondrial Proteins MeSH
- Adolescent MeSH
- Molecular Chaperones MeSH
- Mutation MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Prognosis MeSH
- Proteins genetics MeSH
- Sequence Deletion MeSH
- Carrier Proteins MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
- Poland MeSH
- Slovakia MeSH
- Names of Substances
- Membrane Proteins MeSH
- DNA, Mitochondrial MeSH
- Mitochondrial Proteins MeSH
- Molecular Chaperones MeSH
- Proteins MeSH
- SCO2 protein, human MeSH Browser
- Surf-1 protein MeSH Browser
- Carrier Proteins MeSH
A retrospective, multicenter study of 180 children with cytochrome c oxidase (COX) deficiency analyzed the clinical features, prognosis, and molecular bases of the COX deficiency. Clinical symptoms including failure to thrive, encephalopathy, hypotony, Leigh syndrome, cardiac involvement, and hepatopathy appeared in most patients early after birth or in early childhood. Two thirds of all children died. Biochemical examination revealed an isolated COX deficiency in 101 children and COX deficiency combined with disturbances of other respiratory chain complexes in 79 children. Blood and cerebrospinal fluid lactate increased in 85% and 81% of examined cases, respectively. Pathogenic mutations in mitochondrial or nuclear DNA were established in 75 patients. Mutations in surfeit locus protein 1 gene (SURF1) were found in 47 children with Leigh syndrome; 2bp deletion 845-846delCT was found in 89% of independent alleles. Mutations in a mitochondrial copper-binding protein (SCO2) gene were found in nine children with encephalomyopathy and/or cardiomyopathy; all of them were homozygotes or heterozygotes for 1541G>A mutation. Different mitochondrial DNA (mtDNA) deletion or depletion were found in nine children, mtDNA mutation 3243A>G in six, mtDNA mutation 8363G>A in two children with Leigh syndrome and mtDNA mutations 8344A>G, and 9205-9206delTA in one child each. COX deficiency represents a heterogeneous group of diseases with unfavorable prognosis. Marked prevalence of two nuclear DNA mutations (845-846delCT in the SURF1 gene and 1541G>A in the SCO2 gene) associated with COX deficiency in a Slavonic population suggests the existence of regional differences in the genetic basis of COX deficiency.
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